title: Increased metalloprotease activity in the epileptogenic lesion--Lobectomy reduces metalloprotease activity and urokinase-type uPAR circulating levels.
abstract: Inflammation influences the pathogenesis of seizures by boosting neuronal degeneration of temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). This work aimed to determine the activity of metalloproteases (MMPs) in brain tissue fragments of TLE-HS patients and the effect of lobectomy on circulating inflammatory biomarkers. Surgical fragments (n=4) from epileptogenic focus (EF) e perilesion area (PL), and control hippocampus from autopsy (n=5) were processed for glial protein (GFAP), activated microglia (IB4) immunohistochemistry, and metalloprotease activity (MMP-2, -9). Perilesional area showed GFAP positive cells with morphology of activate astrocyte and reactive gliosis nearby the lesion. In the lesion foci, astrocytes had altered cytoarchitecture with disorganized stroma suggestive of necrosis, and numerous mononuclear cells with few projections and morphological characteristics of activate microglia. Analysis of MMP-9 and MMP-2 in the sera before and after hippocampectomy confirmed the inflammatory pattern of TLE-HS, with high MMP-9 activity; high MMP-9/TIMP-1 and urokinase uPAR plasma levels before lobectomy but low after surgery. Maintenance of MMP-2 activity indicates persistent tissue remodeling in both groups. The present work shows that patients with chronic and medically intractable TLE-HS that undergone amigdalo-hippocampectomy for removal of epileptogenic lesion had a clinical enduring benefit of lack seizure recurrence for up to a year, and consistent reduction of proteases (MMP-9 and uPAR) activation that participate as important inflammatory epileptogenic inducers.
authors.affiliation: Department of Cellular and Molecular Biology, Fluminense Federal University, Niteroi, Rio de Janeiro 24020-141, Brazil. Electronic address: tquirico@vm.uff.br.
authors.forename: Thereza
authors.initials: T
authors.lastname: Quirico-Santos
authors.forename: Angélica
authors.initials: A
authors.lastname: Nascimento Mello
authors.forename: Aline
authors.initials: A
authors.lastname: Casimiro Gomes
authors.forename: Lian Pontes
authors.initials: LP
authors.lastname: de Carvalho
authors.forename: Jorge Marcondes
authors.initials: JM
authors.lastname: de Souza
authors.forename: Soniza
authors.initials: S
authors.lastname: Alves-Leon
mesh_terms: D000293:Adolescent; D000328:Adult; D038481:Anterior Temporal Lobectomy; D016207:Cytokines / Q000097:blood; D004660:Encephalitis / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000097:blood / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000097:blood*; D008875:Middle Aged; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood; D055815:Young Adult
chemical_list: D016207:Cytokines; D055293:Receptors, Urokinase Plasminogen Activator; D019714:Tissue Inhibitor of Metalloproteinases; D045726:Metalloproteases
keywords: Lobectomy; Mesial temporal lobe epilepsy; Metalloprotease; Neuroinflammation; Seizure